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Abstract:

An ultrasonic transducer device for producing ultrasonic beams comprises
a body vibratable at ultrasonic frequencies and an extensive surface for
beam emanation, the device configured to produce an unfocused, or
alternatively a focused, power beam for tissue ablation, the power beam
being produced by vibration over the body of the transducer and emanating
from the extent of the surface, whereby the extensive surface becomes
subject to convective cooling when immersed in a fluid by a chimney
effect set up by said unfocused beam.

Claims:

1. An ultrasonic transducer device for producing ultrasonic beams,
comprising a body vibratable at ultrasonic frequencies and an extensive
surface for beam emanation, the device configured to produce an unfocused
power beam for tissue ablation, the unfocused power beam being produced
by vibration over the body of the transducer and emanating from said
extensive surface, whereby the extensive surface becomes subject to
convective cooling when immersed in a fluid by a chimney effect set up by
said unfocused beam.

2. The device of claim 1, being mounted on a PCB, wherein trenches are
constructed in the PCB for fluid flow to enhance said cooling.

3. The device of claim 1, further comprising a pump unit for actively
pumping liquid around said transducer.

4. The device of claim 1, wherein said ultrasonic transducer device
comprises a piezoelectric element and wherein said vibratable body is a
body of said piezoelectric element.

5. The device of claim 2, comprising an gas-filled gap between said
transducer and said PCB.

6. The device of claim 5, wherein said gas-filled gap is unsealed and
wherein surface tension retains air within said gap when said device is
immersed in fluid.

7. The device of claim 6, further comprising conductive connections to
the PCB across the gas-filled gap, wherein said conductive connections
provide thermal linkage between said transducer and said PCB, thereby
enabling the PCB to act as an additional heat dissipation surface for
said device.

8. The device of claim 1 located at a circumferential wall of a catheter
or at the end of said catheter, and thermally connected to a heat sink
that is located within the catheter and/or at the circumferential wall of
the catheter or in the blood flow.

9. The device of claim 1, located at a circumferential wall of a catheter
or at the end of said catheter, and wherein saline is pumped down the
catheter to provide additional fluid flow around the transducer and/or
around the heat sink.

10. The device of claim 1, further comprising a temperature sensor
located in association with said transducer.

11. The device of claim 10, wherein said temperature sensor is located
downstream of said transducer in a flow direction of liquid in a vessel
within which said device is placed, thereby to measure temperature of
liquid that has passed said extensive surface.

12. The device of claim 10, further comprising a controller for providing
said power beam in a duty cycle, said controller being configured to
modify said duty cycle and/or applied power in response to changes in
temperature indicated by said temperature sensor.

13. The device of claim 12, wherein said controller is configured to
modify said duty cycle to control said surface to remain within a range
of 40.degree. C. to 50.degree. C., or at 44.degree. C.

14. The device of claim 10, controllable to stop said power beam when a
temperature sensed by said sensor reaches or exceeds a predetermined
safety threshold.

15. The device of claim 1, located at the end of a catheter, and further
comprising a temperature sensor located in association with said
transducer, wherein saline is pumped down the catheter to provide fluid
flow around the transducer and wherein a rate of pumping is controlled
according to changes in temperature sensed by said temperature sensor.

16. The device of claim 15, wherein said controller is configured to
modify said rate of pumping to control said surface to remain within a
range of 40.degree. C. to 50.degree. C., or at 44.degree. C.

17. The device of claim 1, wherein said power beam is provided at a
frequency of at least 8 Megahertz, and said vibratable body has a
thickness not exceeding 0.3 millimeters, thereby to increase heat
transfer from the element.

18. The device of claim 1 further comprising a distancing mechanism for
positioning said transducer at least a minimal distance away from a
cavity wall.

19. The device of claim 1, further comprising a controllable valve
openable into a body lumen for controlling fluid flow about said device.

20. The device of claim 1, further comprising a Tec cooler device.

21. The device of claim 1, further comprising metal channels in a PCB.

22. The device of claim 1, further comprising a distancing device for
distancing the transducers from a vessel wall.

23. An ultrasonic transducer device for producing ultrasonic beams,
comprising a body vibratable at ultrasonic frequencies and a surface for
beam emanation, the device configured to produce an unfocused power beam
over an extent of said surface for tissue ablation, the unfocused power
beam being at a frequency of at least 8 Megahertz.

24. The device of claim 22, having a thickness below 0.3 millimeters or a
thickness of 0.15 millimeters, thereby to increase heat transfer from the
element.

25. An ultrasonic transducer device for producing ultrasonic beams,
comprising a body vibratable at ultrasonic frequencies, the device
configured to produce a focused power beam for tissue ablation, the
focused power beam being produced by vibration over the body of the
transducer whereby a surface of said transducer becomes subject to
convective cooling when immersed in a fluid by a chimney effect set up by
said focused beam.

26. An ultrasonic transducer device for producing ultrasonic beams,
comprising a body vibratable at ultrasonic frequencies and an extensive
surface for beam emanation, the device configured to produce an unfocused
power beam for tissue ablation, the unfocused power beam being produced
by vibration over the body of the transducer and emanating from said
extensive surface, the device further comprising a heatsink thermally
coupled to said body for dissipating heat from said device.

27. The ultrasonic transducer device of claim 26, wherein said heatsink
comprises braiding along a wall of a catheter to which said device is
attached.

28. An ultrasonic transducer device for producing ultrasonic beams,
comprising a body vibratable at ultrasonic frequencies and an extensive
surface for beam emanation, the device configured to produce an unfocused
power beam for tissue ablation, the unfocused power beam being produced
by vibration over the body of the transducer and emanating from said
extensive surface, the device further comprising a thermo-electric cooler
device thermally coupled to said body for cooling said body.

29. An ultrasonic transducer device for producing ultrasonic beams,
comprising a body vibratable at ultrasonic frequencies and an extensive
surface for beam emanation, the device configured to produce an unfocused
power beam for tissue ablation, the unfocused power beam being produced
by vibration over the body of the transducer and emanating from said
extensive surface, the body being mounted on a printed circuit board, and
the printed circuit board having channels therein for allowing fluid flow
to cool said body.

30. An ultrasonic transducer device for producing ultrasonic beams,
comprising a body vibratable at ultrasonic frequencies and an extensive
surface for beam emanation, the device configured to produce an unfocused
power beam for tissue ablation, the unfocused power beam being produced
by vibration over the body of the transducer and emanating from said
extensive surface, further comprising a pump for pumping fluid around
said device to cool said device.

31. The ultrasonic transducer device of claim 30, attached to a catheter
and wherein said pump is located within said catheter.

32. An ultrasonic transducer device for producing ultrasonic beams,
comprising a body vibratable at ultrasonic frequencies and an extensive
surface for beam emanation, the device configured to produce an unfocused
power beam for tissue ablation, the unfocused power beam being produced
by vibration over the body of the transducer and emanating from said
extensive surface, the device being insertable into vessels where flow is
present, and further comprising a flow directing structure for directing
said flow present in the vessel over the vibratable body and/or the heat
sink in order to cool said device.

33. The device of claim 32, wherein said flow-directing structure
comprises a balloon.

34. The device of claim 32, wherein said flow directing structure
comprises a shaft and a bending zone on the shaft, the bending zone
directing said flow.

Description:

RELATIONSHIP TO EXISTING APPLICATIONS

[0001] This application claims the benefit of priority under 35 USC 119(e)
of U.S. Provisional Patent Application No. 61/393,947 filed Oct. 18,
2010, the contents of which are incorporated herein by reference in their
entirety.

FIELD AND BACKGROUND OF THE INVENTION

[0002] The present invention relates to an ultrasound transducer device
and cooling thereof and, more particularly, but not exclusively to the
cooling of such a transducer device within a small vessel which may be
filled with fluid, such as a blood vessel or other body lumen.

[0003] Sverdlik et al, in PCT/IL2008/000234, filed Feb. 21, 2008 disclose
a method of using ultrasonic energy for surgical procedures. In a
procedure for stabilizing blood vessel wall abnormality, ultrasonic
heating is carried out of at least a portion of the blood vessel wall
having the abnormality. A parameter is monitored relating to a property
of at least a portion of the heated portion of the blood vessel wall; and
heating is stopped when the monitored parameter changes by a
predetermined factor or after the monitored parameter changes at a slow
enough rate.

[0004] Maguire and Peacock, in EP 1769759 disclose an air backed
ultrasonic transducer. Specifically they disclose an ultrasound
transducer mounted onto a delivery member, such as the elongate body of a
catheter shaft, without a support structure bridging between a separation
area between the transducer and the shaft. Mounting flanges extend from
either end of the transducer and are mounted at first and second
locations along the catheter shaft such that the transducer is not in
mechanical contact with the catheter shaft between those mounting
locations to provide for air backing between the transducer and the
catheter shaft so as to isolate ultrasound transmission radially away
from the catheter shaft and toward the tissue surrounding the shaft. In
Maguire and Peacock, sealing of the transducer ensures that body fluids
such as blood do not displace the air.

[0005] An ultrasound transducer can in principle be used to provide a high
power ultrasound beam that can ablate tissues. However the transformation
of electrical energy into ultrasound is inefficient and considerable heat
is generated at the transducer. The heat needs to be safely dissipated
without causing damage to the blood vessel itself, and standard heat sink
structures cannot be used in blood flow because heat exchange fins can
damage platelets and cause clotting. In general the transducer may be
expected to heat the artery wall as well as the more distant features it
is intended to ablate.

[0006] Furthermore, ultrasound transducers are typically ceramics with
piezoelectric properties. Ceramics have low thermal conductivity and thus
operation at high power causes relatively large heat differentials across
the transducer which often causes cracking.

SUMMARY OF THE INVENTION

[0007] The present embodiments may provide a transducer which carries out
tissue ablation using an unfocused beam from an extended surface of the
transducer. The beam heats surrounding fluid and sets up a chimney effect
which then serves to cool the transducer surface.

[0008] The use of higher frequencies, in excess of 8 Megahertz, allows for
thinner transducers to be used, which reduces the likelihood that large
heat differentials will form or cause cracking. The thicknesses used are
between 100-200 microns, and higher energies result from the higher
frequencies used. The ultrasonic energy may be focused or unfocussed.

[0009] According to one aspect of the present invention there is provided
an ultrasonic transducer device for producing ultrasonic beams,
comprising a body vibratable at ultrasonic frequencies and an extensive
surface for beam emanation, the device configured to produce an unfocused
power beam for tissue ablation, the unfocused power beam being produced
by vibration over the body of the transducer and emanating from said
extensive surface, whereby the extensive surface becomes subject to
convective cooling when immersed in a fluid by a chimney effect set up by
said unfocused beam.

[0010] The device may be mounted on a PCB, wherein trenches are
constructed in the PCB for fluid flow to enhance said cooling.

[0011] The device may comprise a pump unit for actively pumping liquid
around said transducer.

[0012] In an embodiment, said ultrasonic transducer device comprises a
piezoelectric element and wherein said vibratable body is a body of said
piezoelectric element.

[0013] The device may comprise an gas-filled gap between said transducer
and said PCB.

[0014] In an embodiment, said gas-filled gap is unsealed and wherein
surface tension retains air within said gap when said device is immersed
in fluid.

[0015] The device may comprise conductive connections to the PCB across
the gas-filled gap, wherein said conductive connections provide thermal
linkage between said transducer and said PCB, thereby enabling the PCB to
act as an additional heat dissipation surface for said device.

[0016] The device may be located at a circumferential wall of a catheter
or at the end of said catheter, and thermally connected to a heat sink
that is located within the catheter and/or at the circumferential wall of
the catheter or in the blood flow.

[0017] The device may be located at a circumferential wall of a catheter
or at the end of said catheter, and wherein saline is pumped down the
catheter to provide additional fluid flow around the transducer and/or
around the heat sink.

[0018] The device may comprise a temperature sensor located in association
with said transducer.

[0019] In an embodiment, said temperature sensor is located downstream of
said transducer in a flow direction of liquid in a vessel within which
said device is placed, thereby to measure temperature of liquid that has
passed said extensive surface.

[0020] The device may comprise a controller for providing said power beam
in a duty cycle, said controller being configured to modify said duty
cycle and/or applied power in response to changes in temperature
indicated by said temperature sensor.

[0021] In an embodiment, said controller is configured to modify said duty
cycle to control said surface to remain within a range of 40° C.
to 50° C., or at 44° C.

[0022] The device may be controllable to stop said power beam when a
temperature sensed by said sensor reaches or exceeds a predetermined
safety threshold.

[0023] The device may be located at the end of a catheter, and may
comprise a temperature sensor located in association with said
transducer, wherein saline is pumped down the catheter to provide fluid
flow around the transducer and wherein a rate of pumping is controlled
according to changes in temperature sensed by said temperature sensor.

[0024] In an embodiment, said controller is configured to modify said rate
of pumping to control said surface to remain within a range of 40°
C. to 50° C., or at 44° C.

[0025] In an embodiment, said power beam is provided at a frequency of at
least 8 Megahertz, and said vibratable body has a thickness not exceeding
0.3 millimeters, thereby to increase heat transfer from the element.

[0026] An embodiment may comprise a distancing mechanism for positioning
said transducer at least a minimal distance away from the cavity wall.

[0027] An embodiment may comprise a controllable valve openable into a
body lumen for controlling fluid flow about said device.

[0028] An embodiment may comprise a thermoelectric, or Tec, cooler device
to actively enhance cooling.

[0029] The device may include metal channels in a PCB, to allow liquid
flow to cool the device.

[0030] A distancing device may distance the transducers from a vessel
wall, to allow liquid flow in between the device and wall, both for
cooling the device and the wall. In this way the vessel wall is not
damaged by the ultrasound beam.

[0031] According to a further aspect of the present invention there is
provided an ultrasonic transducer device for producing ultrasonic beams,
comprising a body vibratable at ultrasonic frequencies and a surface for
beam emanation, the device configured to produce an unfocused power beam
over an extent of said surface for tissue ablation, the unfocused power
beam being at a frequency of at least 8 Megahertz.

[0032] The device may have a thickness below 0.3 millimeters or a
thickness of 0.15 millimeters, thereby to increase heat transfer from the
element.

[0033] According to a further aspect of the present invention there is
provided an ultrasonic transducer device for producing ultrasonic beams,
comprising a body vibratable at ultrasonic frequencies, the device
configured to produce a focused power beam for tissue ablation, the
focused power beam being produced by vibration over the body of the
transducer whereby a surface of said transducer becomes subject to
convective cooling when immersed in a fluid by a chimney effect set up by
said focused beam.

[0034] According to a yet further aspect of the present invention there is
provided an ultrasonic transducer device for producing ultrasonic beams,
comprising a body vibratable at ultrasonic frequencies and an extensive
surface for beam emanation, the device configured to produce an unfocused
power beam for tissue ablation, the unfocused power beam being produced
by vibration over the body of the transducer and emanating from said
extensive surface, the device further comprising a heatsink thermally
coupled to said body for dissipating heat from said device.

[0035] In an embodiment, said heatsink comprises braiding along a wall of
a catheter to which said device is attached.

[0036] According to a further aspect of the present invention there is
provided an ultrasonic transducer device for producing ultrasonic beams,
comprising a body vibratable at ultrasonic frequencies and an extensive
surface for beam emanation, the device configured to produce an unfocused
power beam for tissue ablation, the unfocused power beam being produced
by vibration over the body of the transducer and emanating from said
extensive surface, the device further comprising a thermo-electric cooler
device thermally coupled to said body for cooling said body.

[0037] According to a further aspect of the present invention there is
provided an ultrasonic transducer device for producing ultrasonic beams,
comprising a body vibratable at ultrasonic frequencies and an extensive
surface for beam emanation, the device configured to produce an unfocused
power beam for tissue ablation, the unfocused power beam being produced
by vibration over the body of the transducer and emanating from said
extensive surface, the body being mounted on a printed circuit board, and
the printed circuit board having channels therein for allowing fluid flow
to cool said body.

[0038] According to a further aspect of the present invention there is
provided an ultrasonic transducer device for producing ultrasonic beams,
comprising a body vibratable at ultrasonic frequencies and an extensive
surface for beam emanation, the device configured to produce an unfocused
power beam for tissue ablation, the unfocused power beam being produced
by vibration over the body of the transducer and emanating from said
extensive surface, further comprising a pump for pumping fluid around
said device to cool said device.

[0039] An embodiment may be attached to a catheter and said pump may be
located within said catheter.

[0040] According to a further aspect of the present invention there is
provided an ultrasonic transducer device for producing ultrasonic beams,
comprising a body vibratable at ultrasonic frequencies and an extensive
surface for beam emanation, the device configured to produce an unfocused
power beam for tissue ablation, the unfocused power beam being produced
by vibration over the body of the transducer and emanating from said
extensive surface, the device being insertable into vessels where flow is
present, and further comprising a flow directing structure for directing
said flow present in the vessel over the vibratable body and/or the heat
sink in order to cool said device.

[0041] In an embodiment, said flow-directing structure comprises a
balloon.

[0042] In an embodiment, said flow directing structure comprises a shaft
and a bending zone on the shaft, the bending zone directing said flow.

[0043] Unless otherwise defined, all technical and scientific terms used
herein have the same meaning as commonly understood by one of ordinary
skill in the art to which this invention belongs. The materials, methods,
and examples provided herein are illustrative only and not intended to be
limiting.

[0044] The word "exemplary" is used herein to mean "serving as an example,
instance or illustration". Any embodiment described as "exemplary" is not
necessarily to be construed as preferred or advantageous over other
embodiments and/or to exclude the incorporation of features from other
embodiments.

[0045] The word "optionally" is used herein to mean "is provided in some
embodiments and not provided in other embodiments". Any particular
embodiment of the invention may include a plurality of "optional"
features unless such features conflict.

[0046] Implementation of the method and/or system of embodiments of the
invention can involve performing or completing selected tasks manually,
automatically, or a combination thereof. This refers in particular to
tasks involving control of the ultrasonic system.

[0047] Moreover, according to actual instrumentation and equipment of
embodiments of the method and/or system of the invention, selected tasks
may be implemented by hardware, by software or by firmware or by a
combination thereof using an operating system.

[0048] For example, hardware for performing selected tasks according to
embodiments of the invention may be implemented as a chip or a circuit.
As software, selected tasks according to embodiments of the invention
could be implemented as a plurality of software instructions being
executed by a computer using any suitable operating system. In an
exemplary embodiment of the invention, one or more tasks according to
exemplary embodiments of method and/or system as described herein are
performed by a data processor, such as a computing platform for executing
a plurality of instructions. Optionally, the data processor includes a
volatile memory for storing instructions and/or data and/or a
non-volatile storage, for example, a magnetic hard-disk and/or removable
media, for storing instructions and/or data. Optionally, a network
connection is provided as well. A display and/or a user input device such
as a keyboard or mouse are optionally provided as well.

BRIEF DESCRIPTION OF THE DRAWINGS

[0049] The patent or application file contains at least one drawing
executed in color. Copies of this patent or patent application
publication with color drawing(s) will be provided by the Office upon
request and payment of the necessary fee.

[0050] The invention is herein described, by way of example only, with
reference to the accompanying drawings. With specific reference now to
the drawings in detail, it is stressed that the particulars shown are by
way of example and for purposes of illustrative discussion of the
preferred embodiments of the present invention only, and are presented in
order to provide what is believed to be the most useful and readily
understood description of the principles and conceptual aspects of the
invention. In this regard, no attempt is made to show structural details
of the invention in more detail than is necessary for a fundamental
understanding of the invention, the description taken with the drawings
making apparent to those skilled in the art how the several forms of the
invention may be embodied in practice.

[0051] In the drawings:

[0052]FIG. 1 is a simplified schematic diagram of a first embodiment of
an ultrasound transducer providing a power beam over a surface extent
according to the present invention;

[0053] FIG. 2 is a simplified schematic diagram illustrating the chimney
effect set up by the ultrasound beam shown in FIG. 1;

[0054] FIG. 3 is a simplified diagram showing variations of a PCB on which
to mount the ultrasound transducer, the PCB having channels in various
configurations for improving fluid flow around the transducer, according
to embodiments of the present invention;

[0055] FIG. 4 is a simplified diagram illustrating an ultrasonic
transducer in a catheter centered in a vessel or cavity using a balloon,
according to embodiments of the present invention;

[0056] FIG. 5 is a simplified diagram illustrating an ultrasonic
transducer in a catheter centered in a vessel or cavity using a coiled
placing wire, according to embodiments of the present invention;

[0057] FIG. 6 is a simplified diagram illustrating an ultrasonic
transducer in a catheter centered in a vessel or cavity using a placing
net, according to embodiments of the present invention;

[0058] FIG. 7 is a simplified diagram illustrating an ultrasonic
transducer located in a window in the circumferential wall of a catheter,
according to embodiments of the present invention;

[0059]FIG. 8 is a simplified block diagram illustrating a catheter and
the control and operating elements that together with the catheter form
an ablation system for use in embodiments of the present invention;

[0060] FIG. 9 is a simplified flow chart illustrating a duty cycle control
loop for controlling the duty cycle based on measured temperature,
according to embodiments of the present invention;

[0061]FIG. 10 is a simplified schematic diagram illustrating a flow
control device for controlling blood flow around the transducer,
according to embodiments of the present invention;

[0062]FIG. 11 is a simplified graph showing correlation between increase
of voltage and increase in temperature during operation of the power
ultrasound beam according to embodiments of the present invention;

[0063] FIG. 12 is a simplified block diagram illustrating a variation of
the device of FIG. 1 in which a thermo-electric cooler and a heat sink
are used on a transducer, the transducer being mounted at a window of a
catheter, according to embodiments of the present invention;

[0064] FIGS. 13A and 13B are simplified schematic diagrams illustrating
variant rectangular and other shapes shown in cross section, of a
piezoelectric element for the transducer of FIG. 1;

[0065] FIG. 14 is a simplified diagram showing cylinder-based shapes shown
in three dimensions of a piezoelectric element for the transducer of FIG.
1;

[0066] FIG. 15A is a side view of a series of piezoelectric elements
mounted on a single mounting according to an embodiment of the present
invention;

[0067] FIG. 15B is a view from above of an arrangement of piezoelectric
elements mounted in two rows according to embodiments of the present
invention;

[0068] FIG. 16 is a simplified schematic diagram that illustrates a series
of angles and positions in relation to a body vessel and a catheter, in
which the transducer can be placed by navigation;

[0069] FIG. 17 is a histology slide using H&E stain, and showing the
thermal effect in a pig carotid artery;

[0070] FIG. 18 is a histology slide using H&E stain, and showing the
thermal effect in a pig renal artery;

[0071]FIG. 19 is a histology slide wherein analysis and marking of the
thermal damage area to a pig Carotid Artery is made by a trained
pathologist;

[0072]FIG. 20 is a histology slide wherein analysis and marking of the
thermal damage area to a pig Renal Artery is made by a trained
pathologist;

[0073] FIG. 21 is a histology slide showing analysis and marking of the
blocked Vasa-Vasorum, with arrows placed by a trained pathologist in a
pig Carotid Artery Vasa-Vasorum in the adventitia; and

[0074] FIG. 22 shows two histology slides with analysis and marking of the
thermal damage, or nerve degeneration area, made by trained pathologist,
for a pig renal artery, and nerves in adventitia.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0075] The present embodiments comprise an ultrasound transducer device
and cooling thereof and, more particularly, but not exclusively to the
cooling of such a transducer device within a small vessel which may be
filled with fluid.

[0076] The present embodiments may provide a transducer which carries out
tissue ablation using an ultrasound beam, for example an unfocussed beam
produced over the body of the transducer and emanating from an extensive
surface of the transducer, as opposed to prior art focused beams which
are produced in tightly defined spots. The beam heats surrounding fluid
opposite the extensive surface and sets up a chimney effect which
provides convective cooling to the transducer extensive surface.

[0077] The transducer may be mounted on a PCB and trenches may be
constructed in the PCB for fluid flow to enhance the cooling effect. In
addition pumping methods may be used to enhance the flow of liquid around
the transducer.

[0078] An embodiment uses an airbacked transducer in which surface tension
is used to retain the air in position. Thus the transducer does not need
to be sealed. Connections to the PCB across the airgap may use heat
conductive materials to ensure that the PCB is in thermal contact with
the transducer and thus enabling the PCB to act as an additional heat
dissipation surface. A metal channel may be provided in the PCB.

[0079] The transducer may be located on a catheter, either at a window in
the side wall of the catheter or at the distal tip of the catheter. In
such a case the transducer may be thermally connected to a heat sink that
is located wholly or partly within the catheter. The heat sink can, in
some embodiments, evacuate the heat to the surroundings or to cooling
liquids such as blood. In addition, saline may be pumped down the
catheter to provide additional fluid flow around the transducer and/or
the heat sink, and the heat sink can be part of the shaft of the catheter
as will be explained in greater detail below.

[0080] The transducer may provide a power beam and a measuring beam and a
method is provided for measuring increases in temperature and stopping
operation or changing the duty cycle or/and applied power if overheating
is detected.

[0081] The power beam may be provided at frequencies at or in excess of 20
Megahertz, and using piezoelectric transducers which are below two
millimeters in thickness, to avoid problems with cracking due to
thermally induced stress within the transducer.

[0082] The principles and operation of an apparatus and method according
to the present invention may be better understood with reference to the
drawings and accompanying description.

[0083] Before explaining at least one embodiment of the invention in
detail, it is to be understood that the invention is not limited in its
application to the details of construction and the arrangement of the
components set forth in the following description or illustrated in the
drawings. The invention is capable of other embodiments or of being
practiced or carried out in various ways. Also, it is to be understood
that the phraseology and terminology employed herein is for the purpose
of description and should not be regarded as limiting.

[0084] Reference is now made to FIG. 1, which illustrates an ultrasonic
transducer device 10 for producing ultrasonic beams. Device 10 comprises
a body 12 which is vibratable at ultrasonic frequencies by an input
electrical signal, and a surface 14 which extends over the body, for beam
emanation. The device may produce an unfocused power beam, indicated by
arrows 16, for tissue ablation or like purposes that require relatively
high power. The unfocused power beam is produced by vibration over the
body 12 of the transducer and emanates from over an extent of the
surface. The beam heats fluid opposite the surface and because the
heating effect occurs over the surface extent it sets up a chimney effect
in the fluid. The extent of the surface thus becomes subject to
convective cooling when immersed in a fluid and producing the power beam.

[0085] Reference is made to FIG. 2 which is a simplified schematic diagram
illustrating the chimney effect. Liquid up against the hot surface 14
above the transducer body 12 is heated by the beam and its density is
reduced causing it to be displaced by lower density cooler fluid. The
displacement is in the direction of arrows 18, typically in a direction
normal to the surface 12 being heated as long as the heating effect is
over a surface extent. If the heating is point heating then the chimney
effect is not set up. Cooler liquid is thus sucked in from the sides as
indicated by arrows 20.

[0086] Returning to FIG. 1, and the device may be mounted on a PCB 22. The
ultrasonic transducer device itself may be a piezoelectric element, which
vibrates in response to electrical input and which produces an electrical
output when itself vibrated.

[0087] Connection mountings 26 on the PCB are used to mount the
transducer. The connection mountings allow a gap 28 to be formed between
the transducer and the PCB. As will be explained in greater detail below,
the PCB can be connected to a conductive heat pad or other heat
dissipating mechanism.

[0088] The gap 28 may be air-filled, and may be sealed to retain the air
when the device is immersed in liquid. However the sealing can attenuate
the ultrasonic energy and thus, in an alternative embodiment the gap may
be unsealed. In such an embodiment, surface tension may retain air within
the gap when the device is immersed in fluid.

[0089] The conductive connections 26 to the PCB across the airgap 28 may
provide thermal conductivity as well as electrical conductivity, thereby
enabling the PCB 22 to act as an additional heat dissipation surface.

[0090] Reference is now made to FIG. 3, which shows four exemplary
structures 22.1, 22.2, 22.3 and 22.4, for the PCB. As shown in FIG. 3,
the PCBs 22.1 . . . 22.4 include trenches 24. In the PCB 22.1, the
transducer is mounted between connection mountings 26, and the trenches
24 thus pass underneath the transducer to allow fluid flow under the
transducer to assist with cooling.

[0091] In many cases the transducer is operated in blood vessels such as
arteries where there is significant fluid flow. However other body
vessels may have little or no natural flow within them, in which case a
pumping mechanism or pumping unit may be provided for actively pumping
liquid around the transducer. In some cases, even arteries may require
some augmentation to the fluid flow via artificial pumping.

[0092] Referring generally to FIGS. 4, 5 and 6, the transducer device 10
is typically inserted into a body vessel using a catheter 40, and in use
is located at a window in the catheter, which window is in these cases on
the circumferential wall close to the distal end of the catheter.
Alternatively the device could be placed on the distal end itself of the
catheter.

[0093] Pumping of saline down the catheter may provide the artificial
pumping referred to above. The transducer device may be thermally
connected to a heat sink that is located within the catheter. Typically
cooling fins cannot be used in blood flow due to the danger of breaking
platelets and causing thrombus, or blood clots. Thus the heat sink may be
retained wholly within the catheter. Saline may be pumped down the
catheter to provide fluid flow around the transducer and around the
heatsink.

[0094] Braiding may be provided in the catheter, say using copper stripes
or stainless still braiding, to use the entire length of the catheter as
a heat sink surface.

[0095] In FIG. 4, the catheter is held in place in the middle of the
vessel away from the wall by a balloon 42. In FIG. 5 a spring 44 keeps
the catheter centered with respect to the wall. The spring may be made of
Nitinol, a shape memory alloy which can be inserted flat and then when
attaining a pre-set temperature reassumes its remembered shape. In FIG. 6
a placing net is used to position the catheter with respect to the wall.

[0096] Distancing the transducer from the vessel wall ensures that the
transducer does not directly heat the vessel wall. Furthermore the
distance allows for fluid flow around the transducer and thus allows the
chimney effect to occur. Furthermore the distance allows for blood flow
at the wall of the vessel thus allowing the epithelium cells at the wall
of the blood vessel to be cooled by the flow of blood and thus not be
damaged by the heating effect of the ultrasound beam. Damaged epithelium
cells are a future risk for the blood vessel. In general the thermal
damage effect that the ultrasound beam uses is the denaturation of
collagen, which occurs at around 55° C. The blood flow is
generally sufficient to ensure that the epithelium layer does not reach
this temperature.

[0097] Reference is now made to FIG. 7, which shows a transducer 70
mounted in a window 72 of a catheter. The chimney effect around the
transducer can have the additional effect of sucking in injected
medication or staining substances from the catheter through the window
72, thus improving injection efficiency.

[0098] A temperature sensor may be provided with the transducer.
Typically, the sensor is placed just downstream of the transducer in the
blood flow direction. Thus the temperature that is measured is that of
liquid that has just passed the transducer surface, and increasing
measured temperature may be taken as an indicator of overheating in the
transducer.

[0099] Reference is now made to FIG. 8, which is a simplified block
diagram of a system according to an embodiment of the present invention.
In FIG. 8, the system 110 may contain an acoustic transducer 112, a power
supply unit 114, a control unit 116, a pumping or circulation unit, shown
as perfusion unit 118, a balloon control unit 120, temperature sensor
121, and a navigating shaft 122.

[0100] The navigating unit allows the acoustic element to navigate to the
location or locations at which it is needed. The balloon control unit
controls a balloon for supporting the lumen as needed and centering the
catheter as discussed. The perfusion unit provides injection substances
as necessary.

[0101] Reference is now made to FIG. 9 which is a simplified flow chart to
illustrate how the controller 116 may vary the duty cycle of the power
ultrasound beam in accordance with the temperature measured at
temperature sensor 121. Controller 116 may provide the power beam in a
duty cycle and/or just by controlling a level of applied power. The duty
cycle and/or applied power may be increased if the temperature falls,
kept the same if the temperature remains constant and decreased if the
temperature rises. The duty cycle and/or applied power may for example be
controlled to keep transducer surface 14 within a range of 40° C.
to 50° C., or at 44° C., or at other temperatures as deemed
appropriate.

[0102] The controller 116 may stop the power beam when the temperature
sensed by sensor 121 reaches or exceeds a predetermined safety threshold.

[0103] As explained above, in one embodiment the transducer is located in
a window or at the end of a catheter, and the temperature sensor is used
to control a rate at which cooling saline is pumped down the catheter to
provide fluid flow around the transducer.

[0104] As well as controlling the pumping of saline from the catheter, it
is also possible to control the blood flow rate within the vessel, for
example using a balloon valve. Reference is now made to FIG. 10 in which
a transducer 124 is mounted at a window of catheter 126. A valve flow
control device 128 sits around the catheter and can be opened or closed
to change the blood flow around the transducer.

[0105] As well as saline, contrast agents or medicines may be injected via
the catheter and these too may provide an auxiliary role of helping to
cool the transducer.

[0106] Reference is now made to FIG. 11, which shows temperature
measurements in the upper graph against voltage in the lower graph for a
transducer according to the present embodiments. Specifically, FIG. 11
shows a graph of real time measurements of voltage and temperature in the
renal area. The relation between the applied voltage and the temperature
can easily be observed.

[0107] In addition in the temperature graph falls in temperature for
example at t=350[sec]; 600[sec]; 1150[sec] are seen. These drops are due
to cold (25[° C.]) saline injection. Use of cold saline is an
additional method of cooling that may be used.

[0108] Heat in the transducer is directly proportional to voltage. In
addition the heat is directly proportional to the reciprocal of impedance
and to the efficiency subtracted from unity. Heat is additionally
proportional to the liquid flow over the transducer surface. The above
may be expressed algebraically as:

[0109] heat↑αV↑/Z*(1-eff) and
heat↑αflow↓.

[0110] The blood flow rate may be calibrated with the heating and cooling
effects. Thus it may be possible to turn on the transducer, check the
temperature, check the flow rate, and then use a calibration table to
provide the correct cooling.

[0111] Reference is now made to FIG. 12, which is a simplified diagram
illustrating an embodiment of the present transducer device in which
additional cooling elements are provided. Located at window 130 of
catheter 132, a transducer 134 is connected to a thermoelectric or
peltier cooler 136 which in turn is connected to a heat sink 138. Typical
dimensions for the construction are 0.8 mm overall, wherein 0.5 mm is the
thickness of the heat sink. Alternatively, the TEC and\or the heat sink
may be placed in the axial direction of the catheter or as part of the
catheter shaft. It is noted that if attempting to use high power
ultrasound over the entire body of a piezoelectric element, there is a
problem with breakage of the transducer due to thermal differences within
the element. Ceramics generally have low thermal conductivity.

[0112] The present embodiments avoid the above problem by using relatively
high frequencies, in the range of 8 or 10 to 40 MHz, which permits the
use of thinner ceramics, so that the issue of thermal differences does
not arise, or at least does not lead to breakage of the elements.
Specifically, a frequency range of 10-40 MHz provides heating effects
over a range of millimeters, and has been used for imaging but not at
high power for ablation. The thinner ceramics are less than 0.25 mm in
thickness and an example uses 0.15 mm.

[0113] As mentioned with reference to FIG. 9, control may be achieved by
managing either the duty cycle or the applied power.

[0114] To date, imaging has used unfocused beams but at low power, whereas
ablation has used high power beams which have always been at lower
frequencies and focused. Imaging uses short pulses followed by gaps to
listen to the echo. Ablation uses continuous or long bursts in a duty
cycle. Imaging to follow the results may be carried out during the gaps
in the duty cycle.

[0115] As mentioned above, the duty cycle can be changed as part of a
control loop to maintain the correct temperature at the transducer
surface.

[0116] Imaging can be used to obtain the face of the vessel or lumen wall
and thus to provide a further control loop to make sure that the
transducer is kept away from the wall.

[0117] The present embodiments are now considered in greater detail. The
present embodiments relate generally to devices, parameters and methods
for the treatment of tissue using ultrasonic waves in particular for
heating, at a target area such as in the wall of a tube or cavity,
located in the living body. The treatment may involve excitation using
high power acoustic energy.

[0118] The ultrasonic effect is achieved in such a way that there is
control over the heated target tissue volume and location. Preferably, a
controlled volume of tissue between the ultrasonic element and the target
tissue, is not treated. This distal effect may be achieved without the
need of mechanical contact with the cavity walls.

[0119] Detailed application of the above includes the ability to cause
moderate thermal damage within a controlled volume at the outer side of a
cavity wall without damaging the inner side of the vessel, the inner side
including different types of epithelium.

[0120] The treatment method may be applied by creating a gradient of
different temperatures in the tissue by the combined effects of: heating
the tissue with high power ultrasound and cooling of the tissue using
conduction and convection. The convection could be of natural fluid, for
example blood flow, or by artificial injection of cooling liquid, for
example cold saline injection. Additional temperature effects that are
widely elaborated in other sources may also simultaneously influence the
temperature gradient, for example--blood flow or capillary blood
perfusion.

[0121] The heating control is performed by controlling the parameters of
the ultrasonic field and the transmission protocol, including:
transmission frequency, power, duty cycle and duration, as will be
described in greater detail herein.

[0122] The treatment is controlled by feedback from the tissue using an
echo received from the tissue during the treatment. Specifically, at high
temperatures above 55° C. an irreversible change is created in the
collagen fibers in the tissue; this change may be monitored using the
ultrasonic echo from the tissue, which allows mapping of the damaged
tissue area.

[0123] It is also possible to increase or\and to add effects by ejection
of fluids into the treated area or at an upstream area in such a way that
the ejected fluid is inserted into the vessel, typically through the
vasa-vasorum or the adventitia lymph capillary.

[0124] Nevertheless, it is possible to control the flow in the vessel at
different locations using different devices, for example a balloon
opening in the vessel and again changing the treated effects in the
tissue.

[0125] Typically, the ultrasonic transmission is applied at high power,
high frequency and for more than one second. Heating of the tissue in the
ultrasonic field is performed by absorption of the acoustic energy in a
process of dissipation of mechanical energy. The absorption and influence
of the energy on the tissue includes inter alia the following effects: a
heating effect, a mechanical effect, a pressure effect, a sub-pressure
and a cavitation effect.

[0126] Simultaneously with the transmission the cooling effect is achieved
by liquid flow in the vessel or fluid present (for example blood, urine,
lymphatic liquid, bile) or liquid active ejection.

[0127] The present embodiments may provide the possibility of transmitting
the energy to a second side of a wall without touching the wall, for
example a cavity or lumen wall. By not touching it is possible to
increase protection for both the elements and the non target tissue by
allowing fluid to flow on the cavity walls and on the transducer surface.
The liquid provides for cooling. The present embodiments may also allow
for easier operation by not restricting the transducer location.

[0128] The present embodiments may transmit a non-focused acoustic field
to reach the target tissue. An advantage of not having to focus the field
is that there is no need to control the tissue distance from the
transducer. For example renal denervation may be carried out simply by
allowing the catheter to transmit a wide, high power acoustic field from
a nonspecific location in the artery to a distal nonspecific location of
the renal nerve.

[0130] Embodiments of the invention may allow ejection of materials into
the treated area or to an upstream area therefrom in a way that the
materials are inserted into the vessel, say through the vasa-vasorum or
the adventitia lymph capillary.

[0131] The embodiments described herein allow sampling of the voltage
created on the ultrasonic element due to echoes from the tissue and
processing the data in such a way that the treated tissue is monitored.

[0132] Echo sampling and recording and or processing for measurement and
monitoring can be performed simultaneously with the treatment. Such
simultaneous treatment and analysis can increase the level of control of
the treatment in real time and help ensure achievement of the desired
results.

[0133] More specifically, the following information may be monitored from
the echoes received within a vessel:

[0134] wall distance from the transducer,

[0135] vessel layer (media, adventitia, peri-adventitia) position,

[0136] thermal effect in the tissue location and

[0137] area of the thermal effect.

[0138] The data analysis method may include echo intensity, backscatter,
spectral signature mapping, elastography, classification according to
classification matrix of tissues, and the ultrasonic effect.

[0139] The control unit may use the above data and analysis for increasing
the treatment, or reducing the treatment, or stopping the treatment, or
providing indications regarding the treatment stage, or providing
indications to stop or to continue the treatment.

[0140] A therapeutic catheter with an ultrasonic transducer may allow for
transmission to the vessel from the inner side.

[0141] An ultrasonic transducer may be placed in proximity to a wall, with
an internal catheter and transmission to the outer side of the wall. In
the case of limbs one transducer can be placed externally on the outside
of the skin and another in a blood vessel.

[0142] An endoscope system may include an ultrasonic element in its tip.
The endoscope may be inserted through the skin and ultrasonic
transmission may be provided to the outer side of the cavity.

[0143] The fluid control methods may include one or more of the following
implementations:

[0144] A restrictor around the transducer. The implementation may involve:
placing the transducer at a different location in the vessel, and
controlling the flow;

[0145] A restrictor near the transducer. The implementation may again
involve placing the transducer at a different location in the vessel, and
controlling the flow;

[0146] A restrictor in front of (upstream of) the transducer. The method
may involve blocking the flow upstream in order to load the vasa-vasorum
with liquid and particles.

[0147] A restrictor past, that is downstream of, the transducer. The
method may involve blocking the flow downstream of the transducer to
allow drug delivery specifically to the treated area;

[0148] The restrictor may be one or more of the following: a balloon, a
wire, nets, or a thin plastic sheet.

[0149] Manipulation of in the tissue reaction to the ultrasonic treatment
is possible by:

[0150] Injecting vasoconstriction materials into the blood, and in this
way reducing the perfusion and heat evacuation from the tissue, or
injecting or evoking micro-bubbles and increasing the heating by
increasing absorption of the ultrasonic energy, or the evoked
micro-bubbles may be produced by use of an additional separate
transducer.

[0151] Micro-bubble transportation through the cell membrane may be
increased using the acoustic treatment, and may achieve a multiplied
effect.

[0152] The tissue may be cooled before treatment in order to protect and
or control the treated area and non-treated area.

[0153] Artificial opening of a minimal cavity surgery opening in the skin
for insertion of the therapeutic catheter may be provided.

[0154] The ultrasonic field and/or the level of perfusion can be
controlled and manipulated by influencing the body system in general.

[0155] Possible target tissues for the device include one or more of the
following and their nearby tissues to douse cavities: arteries, veins,
lymph vessels, intestine, esophagus, CNS, urine lumen, gall bladder
lumen, Stomach, and Tear Trough.

[0156] Applications for the above-described embodiments include the
following:

[0162] More detailed examples for treatment and advantages using the
present embodiments include phantom pain treatment in which, the target
tissue is nerve tissue in the limbs. The catheter cavity may be located
in a limb artery. The purpose of the treatment may be reducing phantom
pain innervations by denerving the injured nerve.

[0163] A point to note is that the attenuation of the ultrasound field is
smaller in the fatty tissue around the nerves than in the nerves
themselves at the device frequencies. Furthermore the fatty tissue, due
to a relatively low heat conduction, isolates the heat created in the
nerves. Such phenomena increase the selectiveness of the treatment.

[0164] An additional example of treatment is renal denervation.

[0165] In this treatment the target is the renal nerves. The catheter
cavity is located in the renal artery. The purpose is to reduce pressure
on the heart for high blood pressure patients. It is noted that the
frequency, power and acoustic beam as per the data and results
hereinbelow, treat the nerves without or with minimal damage to the
artery. In addition, as in the previous example, the attenuation is
smaller in the fatty tissue around the nerves than in the nerves
themselves at the device frequencies, which increases the selectiveness
of the treatment.

[0166] Possible treatment effects in the tissues can be one or more of the
following:

[0169] Mechanical blocking of the vasa-vasorum or\and the lymph capillary;

[0170] Mechanical changes in the collagen fibers, an increase or decrease
in stiffness and reducing the maximal tension for tearing;

[0171] Biochemical changing in the tissues may include: reducing or
preventing plate connection to collagen, and changes of material
diffusion through the cell walls.

[0172] The device may be operated using typical parameters for acoustic
transmission as follows:

[0173] Transmission frequency: 8-30 MHz;

[0174] imaging frequency 8-60 MHz;

[0175] Transmission intensity (SATA): up to 200 w/cm2;

[0176] Transmission duration (total time): 1-120 seconds.

[0177] The ultrasonic elements transfer the energy to the target tissue,
and may also be used as sensors for receiving reflections from the
tissue.

[0178] The ultrasonic element may also be used as a jet evacuator of
fluids for cooling or/and for drug delivery.

[0179] The ultrasonic element can be used as a microbubble evacuator.

[0180] The ultrasonic element typically includes one or more ultrasonic
transducers including a piezoelectric material 24 or a MEMS element--see
FIGS. 2 and 3. Electrodes may provide power to the transducer. The
housing 30 protects the assembly, and an electrical connection may be
provided between the electrodes and the catheter wires.

[0181] The transducer element 124 may, as mentioned by a piezo-electric
elements or a MEMS element.

[0182] A PIEZO-electric transducer element may typically be made from
PIEZO-electric material, for example: PZT ceramics, PIEZO-electric
quartz.

[0183] Reference is now made to FIGS. 14A, 14B and 14C which illustrate
designs for the ultrasonic element 112. FIG. 14A illustrates a series of
shapes where the depth cross-section is rectangular as shown in element
133. The remaining elements in FIG. 7A are viewed from above. Element 135
is rectangular as seen from above. Element 137 is a hexagon. Element 139
is an irregular quadrilateral. Element 140 is a flattened circle. Element
142 is a trapezium. Element 144 is a bullet shape. Element 146 is a
trapezium having a shorter dimension between its parallel sides than the
trapezium of element 142. Element 148 is a comb shape having a narrow
tooth at a first end followed by three wider teeth. Element 150 is a "W"
shape, again with a narrow tooth projection at a first end.

[0185] FIG. 14C illustrates four variations on a cylindrical element.
Element 156 is a filled cylinder. Element 158 is a cylinder with a
removable sector. Element 160 is a hollow cylinder having an opening 161
in the lower wall, and element 162 is a hollow cylinder having an open
part of the cylinder wall along its length.

[0186] In addition the element 112 (as shown in FIG. 8) may be spherical.

[0187] In embodiments the transducer described above does not necessarily
include a focal point for the ultrasonic beam. As a result the beam can
reach various targets without requiring a precise distance between the
element and the target, as will be described in greater detail below.

[0188] Possible construction of the transducer may comprise regular
coating methods for piezo elements, and coating materials including one
or more of: silver, Ni, gold, copper, or carbon nano-tubes.

[0189] Additional coating of the electrodes may improve one or more of the
following: the electric conductivity, the acoustic matching, the acoustic
reflection or the acoustic amplification.

[0190] The additional coating may use any of a variety of materials
including polymers, glass and metals.

[0191] The PIEZO-electric material may for example comprise:
PIEZO-electric ceramics and/or PIEZO-electric quartz. An embodiment as
discussed hereinbelow with cooling methods may allow the design to use
high hardness ceramics, which have advantages of being of high
efficiency, and being small and cheap.

[0192] MEMS--the acoustic element can also be implemented using MEMS.

[0193] More than one acoustic element can be implemented, for example:

[0194] a phased array matrix of elements;

[0195] a non-linear geometric array;

[0196] a matrix of elements each having different resonant frequencies

[0197] Reference is now made to FIGS. 15A and 15B which illustrate
examples for multi-elements transducers. FIG. 15A is a side view showing
five piezoelectric elements 170 mounted on a curved PCB 172. FIG. 15B is
a view from above showing two rows of piezoelectric elements 174 and 176.

[0198] The housing can made from one or more of the following materials:
metals, ceramics, PZT, PIEZO-electric ceramics, glass, polymers or
carbons.

[0199] The housing may provide an angiogram directional projection for
better placing of the element. The housing may further be shaped to
provide focusing or to affect fluid flow within the lumen around the
element.

[0200] The housing may be designed to provide relatively high heat
transfer from the element in order to avoid overheating. Typically the
heat conductance is a function of shape and of the material used, however
standard cooling fins cannot be used in the blood stream as they may
cause platelets to break, thus causing blood clots.

[0201] The housing can include acoustic damping materials, such as
tungsten, or alternatively may be designed to provide an acoustic
amplifying effect. As per the discussion above, typically some of the
piezoelectric surface is damped and some is provided with acoustic
amplification.

[0202] A drug delivery capsule may be provided to inject materials into
the bloodstream as required by the procedure.

[0203] The printed circuit may comprise materials such as hard polymers,
flexible polymers, glass-fiber and carbon fiber. Alternatively, the
printed circuit may be printed directly on the housing.

[0204] As discussed, connection to the acoustic element may use any of
wire soldering, paste soldering process, conductive gluing and wire
bonding. The connection is preferably both a good heat conductor and a
good electrical conductor.

[0205] The circuit itself may include vias of copper or other metals for
higher heat transfer. One or more printed materials may be provided on
the board, including: copper, metals, polymers, and intermediate
materials.

[0206] Coatings such as metals, PZT, chemical coatings, isolation
coatings, hydrophilic coatings and hydrophobic coatings may be used on
different parts of the PCB or housing.

[0207] The acoustic transducer may be connected to the control unit 116
using different kinds of wires including: coax wire, twisted pair, and
fiber optic cable.

[0208] The acoustic transducer and the catheter may be coated with
different coatings including: an isolation coating, a praline, NiSi,
hydrophobic coating, hydrophilic coating, or any kind of biocompatible
coating,

[0209] As mentioned above, an air pocket may be maintained between the PCB
and the piezoelectric element.

[0210] The acoustic isolation of the piezoelectric element and consequent
increase in efficiency has been mentioned above. This advantage can be
used for working in small cavities in order to improve the ability to
heat the target volume without at the same time heating the transducer
volume.

[0211] Air pockets may be formed by the use of trenches in the PCB
structure as illustrated with reference to FIG. 3. or by providing a
mounting as shown in FIG. 1 where a gap is defined between the
piezoelectric element and the PCB.

[0212] Hydrophobic coatings, including praline, may be used to enhance the
surface tension effect in order to prevent the water medium from
penetrating into the air volume.

[0213] The coating may cover the entire air bubble surrounding or part of
it and prevent water from penetrating in.

[0214] It is noted that the air bubble does not need to be maintained
indefinitely. It is sufficient that it is retained for the duration of
the ultrasound procedure.

[0215] The ultrasonic element may use different anti-resonance values for
the working frequency when available. For example one anti- resonance may
be used for moderate heating of the tissue, another for power heating of
the tissue and yet another for monitoring.

[0216] The device may be able to provide an injection jet to the tissue,
may provide for increasing fluid flow under the element, say to improve
cooling, may evoke micro-bubbles, and may monitor the heating effect and
or any injection. The measurement system may include doppler analysis and
the heat treatment may use focused or unfocused ultrasound.

[0217] In embodiments, the navigation unit 122 may allow the acoustic
element to reach the desired location. The navigation unit may further
have some auxiliary functions. For example it may deliver the power to
the element from the control unit, record measurements from the element
and even deliver the measurements to the control unit 116. The navigation
unit may further be involved in heat absorption or transfer from the
transducer to the ambient or to the surrounding liquids by providing an
additional heat exchange surface extending from the catheter.

[0218] The navigation unit may also mechanically hold and place the
ultrasonic elements in different locations and at different desired
angles, as per FIG. 16. In FIG. 16 a ring configuration 180 may be used,
or an angle configuration 182, or a cylindrical configuration 184 or a
side configuration 186 or a front configuration 188, each in relation to
the catheter.

[0219] In embodiments, the navigation unit may include an external
navigated control unit. Close to the ultrasonic element, a placing unit
may include a balloon, a placing wire or a net or the like.

[0220] A heat sink function may including cooling the ultrasonic unit
using outside fluid including: blood, urine or CSF. The function may
include increasing the heat evacuation by pumping fluid over or from the
acoustic unit surface. The function may involve increasing the heat
evacuation using internal or external heat conductive material,
including: blood passivation coating, or printed coating, or may include
increasing the heat evacuation using an internal or external heat
conductive balloon.

[0221] Heat evacuation may be increased by using an internal or external
heat conductive balloon with heat conduction material.

[0222] The control unit 116 may provide various kinds of closed loop
control and indications on the treatments. The control unit may receive
signals from echoes from the tissue. The echo may indicate the area and
treatment effect, or the echo can indicate the distance from the cavity
wall to the transducer device. The sensor may be a temperature sensor,
which may indirectly sense the temperature of the transducer by measuring
fluid that has just passed the sensor. The temperature may indicate the
treatment efficiency, or efficiency of cooling of the cavity, or the
cooling or heating of the transducer.

[0223] A power sensor can indicate the output treatment energy. A blood
pressure sensor or other like sensors may be provided to indicate
reaction to the treatment. A flow sensor can monitor fluid flow in the
region of the treatment.

[0224] Closed loop effects which do not require the control unit may also
be used, as known to the skilled person, for example a coating material
on the transducer surface may be provided that attaches to particles or
other materials that come from the treated tissue. The attachment may be
used to control the ultrasonic process by making changes to the
transducer frequency during operation.

[0225] Materials that can be inserted into the target tissue volume
include restenosis prevention materials, for treatment of blood vessels,
and materials that are used in drug eluting stents, such as sirolimus,
and paclitaxel.

[0226] Other materials can be used, say in drug exuding and eluding
balloons, and may include materials that are used for bio-degradable
stents, anti-Inflammatory materials, medications that may be better
presented locally to the tissue than systemically, anti-thrombotic
materials, such as Heparin, Aspirin, Ticlopidine, and Clopidogrel, and
materials that can cause damage or death to target tissues. Thus
materials that can cause nerve death may be supplied for renal
denervation.

[0227] Also, materials that may help in blocking of the tissue
micro-circulation in heating, such as polymers that undergo cross
linking, or soluble collagen, or material that may increase the
ultrasonic heating of the tissue, such as micro-bubbles that cause higher
energy absorption, may be used, or in the latter case generated on site.

[0228] Micro-bubble transportation through the cells membrane can be
increased using the acoustic treatment, and achieve a multiplicative
effect.

[0229] Also any kind of medication can be applied.

[0230] The transducer may be positioned on a catheter inside blood-vessels
or blood cavities. Ultrasonic irradiation of the target tissue from
inside the vessel lumen or cavity outwards may then be provided. Cooling
of the piezoelectric element may be achieved by making the design
sufficiently conductive and then using blood flow or flow of a fluid from
an external source, such as saline that is irrigated into the blood
vessel.

[0231] The transducer may be positioned on a catheter inside tissue canals
or cavities of body fluids in the body, such as the urethra or urinary
bladder, or in the spinal cord or brain ventricles (CNS fluid).
Ultrasonic irradiation of the target tissue from inside the canal/cavity
outwards may then be provided.

[0232] The transducer may alternatively be positioned on the tip of an
endoscope or like device. The endoscope is inserted through a small hole
in the skin, and the ultrasonic transducer is positioned on or near the
target tissue.

[0233] For cooling, external irrigation is allowed to flow into the area
of the treatment cavity. The endoscope tip may for example be positioned
inside a balloon like device. The cooling fluid flows inside the balloon.
The balloon is positioned next to the treatment tissue location. The
ultrasonic transducer irradiates the target tissue through the balloon
wall. Alternatively, the balloon may be positioned on the skin and not
inserted through it. The treatment target may be near the skin.

[0234] The ultrasonic transducer may be positioned at a location that
allows ultrasonic irradiation of the target tissue. Irrigation of
required material in a liquid form may be provided into the blood vessels
or lymphatic vessels that supply the perfusion or lymphatic capillaries
of the target tissue volume, for example the artery vasa-vasorum.

[0235] The method may involve waiting a known time constant for the
required material to reach the target tissue.

[0236] It is possible to add micro-bubbles to the fluid material in order
to help with detection of presence of the material in the target tissue.
Micro-bubbles may be detected using ultrasound and sub-harmonic imaging.
Micro-bubbles may also improve heating of the target tissue under
ultrasonic energy, due to higher absorption of the ultrasonic energy in
the tissue volume where they are located.

[0237] Applying a thermal effect in the tissue may cause the capillaries
to be blocked mechanically or by blood coagulation.

[0238] Ultrasound energy applies mechanical force on particles that are
present in a liquid, when there is a difference in the acoustic
impedance, which is a function of the density multiplied by the speed of
sound, between the particles and the liquid. The applied force then
pushes particles along the direction of the traveling ultrasonic waves.
The mechanical force phenomenon can be used to ensure that required
substances arrive at the treatment site.

[0239] The ultrasonic transducer may be positioned in a tissue liquid
cavity such as a blood vessel, near the target tissue, while ensuring a
liquid spacing between the target tissue and the ultrasonic transducer
irradiating face. As mentioned above a control loop can be used to ensure
that the transducer does not touch the vessel wall and damage epithelium
cells.

[0240] The required material may be released into the tissue liquid cavity
in a way that will cause some of the particles to enter the spacing
between the target tissue and the ultrasonic transducer irradiating face.
One way of doing this is to coat the face of the ultrasonic transducer
with the required material, such that the operation of the ultrasonic
transducer may cause particles of the required material to be released
into the surrounding liquid.

[0241] Another possibility is to add micro-bubbles to the required
material fluid in order to detect the material presence in the target
tissue. Micro-bubbles may be detected using ultrasound and sub-harmonic
imaging.

[0242] Yet another possibility is to activate the ultrasonic transducer so
as to apply force on the required material particles to push the
particles into the blood vessel wall near the ultrasonic transducer
irradiating face, using the pushing effect mentioned above.

[0243] Another possibility is to apply the ultrasonic energy in short high
power pulses with long separations between each pulse. This may apply
mechanical force, as per the phenomenon discussed above, to the particles
to push them into the tissue wall, without heating the tissue wall
extensively.

[0244] A further possibility is that activation of the captured required
material can be achieved by applying additional ultrasonic energy or some
other kind of external energy such as a magnetic field on Ferro-electric
particles, or an ultrasonic shock-wave to the particles

[0245] The present embodiments may be used for the treatment of renal
denervation. The transducer is simply positioned at 1, 2 or more
treatment points, and there is no need for tip manipulation or accurate
positioning. The total energizing duration may be between 2 seconds and 2
minutes at each point. Real-time feedback of treatment progress may be
provided. The advantages of ultrasonic treatment include directional,
localized and remote target tissue effects with minimal damage to other
closer tissues, possibly reducing pain, preservation of endothelium and
elastic lamina structure and function, so that there is no post treatment
stenosis, or at least reduced post treatment stenosis, the avoidance of
any mechanical contact on the blood vessel wall, and overall a more
robust treatment effect due to real-time feedback.

[0246] The following table is a summary of currently contemplated clinical
applications.

TABLE-US-00002
TABLE 2
Summary of the Technology
Technology
The ultrasonic transducer:
1.1.1. Very small: 1.5 × 8 [mm]
1.1.2. Very thin: 0.8 [mm]
1.1.3. Very high ultrasonic intensity output: 100 [W/cm{circumflex over
( )}2]
1.1.4. Relatively high work frequencies: 10-25 [MHz].
1.1.5. Biocompatible coating: Perylene
1.2. The catheter
1.2.1. Ultrasonic transducer cooling: vessel blood/liquid flow +
catheter
breading as heat sink
1.2.2. Very flexible treatment tip: 10 mm stiff length. (Pass through 8
Fr
"hokey-stick" guide catheter)
1.2.3. Precise and easy torque following
1.2.4. Standard 0.014 OTW
1.2.5. Relatively small diameter: 6 Fr
1.3. Distancing fixture
1.3.1. Distancing transducer face from artery wall to prevent contact
damage,
with minimal mechanical forces on artery wall
2. Technology functionality
2.1. Non-focused ultrasonic beam-like ultrasonic emission
2.1.1. Simple anatomic
2.1.2. Big treatment volume cross-section, the size of the transducer
face
(differing from focused ultrasound with small treatment volume)
2.1.3. Relatively even spread of ultrasonic energy in beam cross-section
(No
need to precise anatomic positioning like in focused ultrasound)
2.2. Treatment maneuverability and directionality
2.2.1. Simple maneuvering with nearly 1:1 torquability.
2.2.2. Simple treatment beam directivity feedback and control from
standard
angiograph (0, 90, 180, 270)
2.2.3. No need for high operator skills
2.2.4. No problem to use contrast agent during treatment
2.3. Ultrasonic imaging using the unique transducer-Continuous
measurement of distance to artery wall
2.3.1. Treatment tip real positioning measurement (not possible only
from
angiography)
2.3.2. Feedback to prevent high power operation of the transducer while
touching the artery wall.
3. Tissue treatment
3.1. Very fast treatment:
3.1.1. Treatment duration of 30-5 sec per treatment point.
3.1.2. Possibly 4 treatment point per artery for renal denervation
3.2. Remote and localized effect
3.2.1. Thermal effect volume in the tissue far from the transducer face:
media, adventitia, Vasa-Vasorum, peri-adventitia, adventitia nerves,
peri-
adventitia nerves, peri-adventitia capillaries.
3.2.2. Targeting tissues in varying distances from transducer face
according to
treatment parameters (not possible in most focused ultrasonic catheter
designs)
3.2.3. Possibility to apply thermal effect in tissues located 5 mm from
the
lumen wall. Relevant for peripheral nerves blocking from peripheral
arteries.
3.2.4. Non targeted tissues on the beam path to the target tissue are
not
damaged.
3.2.5. Importantly no damage to the endothelium, basal membrane and
internal elastic lamina.
3.3. Tissue selectivity
3.3.1. Highly selective remote thermal effect in nerve bundles that are
covered with thick fat tissue. (most relevant to Renal Denervation in
the
Renal artery ostium)
3.4. Treatment special features for Renal Denervation
3.4.1. Working very close to artery ostium: <10 [mm]
3.4.2. Working in short arteries: <20 [mm]
3.4.3. Working in small arteries: 4-3 [mm]
4. Safety
4.1. The temperature of the blood that flows over the ultrasonic
transducer does
not go over 50 C. while working in the maximal allowed operation
intensity
level 50 [W/cm{circumflex over ( )}2].
4.2. The temperature of the blood that flows over the ultrasonic
transducer does
not go over 43 C. while working in the therapeutic operation intensity
level 30
[W/cm{circumflex over ( )}2]. No need to add external cooling saline
injection.
4.3. The therapeutic treatment on the blood vessel wall is done with no
mechanical
contact with the vessel wall. No danger of damaging the vessel wall or
disrupting any pathologies on the wall (Atherosclerosis plaques)
4.4. Localized and controlled effect specifically in the targeted
treatment volume.
No non-controlled energy effects in other tissues (unlike in RF
treatment).
4.5. No blocking of the blood flow during the treatment
5. Possible implications
5.1. Much less pain in treatment: fast blocking of nerves with no
electric excitation
of the target nerve and no effect on other nerves (In contrast with
Unipolar RF
treatment)

[0248] Reference is now made to FIGS. 17-22 which illustrate experimental
results following use of the device.

[0249] FIG. 17 is a histology slide, using H&E stain, and showing the
thermal effect in a pig carotid artery. The border of the thermal effect
region in the tissue is marked with a dashed line and noted as "Thermal
Damage". The setup used was an ultrasonic catheter from inside the blood
vessel.

[0250] FIG. 18 is a histology slide, using H&E stain, and showing the
thermal effect in a pig renal artery. The border of the thermal effect
region in the tissue is marked with a dashed line and noted as "Thermal".
A necrotic nerve inside the thermal effect region is marked with an arrow
and "necrotic nerve" text. The setup involved an ultrasonic catheter from
inside the blood vessel.

[0251] It is noted that the embodiments cause thermal damage in target
tissues far from the lumen internal wall, while causing no thermal damage
in the lumen wall internal layer.

[0252] Specifically in blood vessels it was shown that thermal damage was
achieved in the adventitia or media layers, without causing any apparent
damage in the intima layer, either the endothelium or the elastic lamina.

[0253] It is believed that the reason for this effect is that the
ultrasonic energy heats the artery wall all along the beam, but the blood
flow in the lumen cools the tissue that is close to the blood flow, thus
the endothelium wall never heats sufficiently to be damaged. It is
possible to find a setting for the treatment parameters so to cause
heating above 55C of the tissues far from the blood flow, while the
temperature of the intima layer is kept below 55C.

[0254] Exemplary results are shown in FIGS. 19 and 20 which are histology
slides wherein analysis and marking of the thermal damage area to a pig
Carotid Artery and a Pig Renal Artery respectively, is made by a trained
pathologist.

[0255] Heating the adventitia or media can cause blocking of the flow
inside the small capillaries (called Vasa-Vasorum) in the blood vessel
media and adventitia, for example by mechanical crimping due to the
shrinking of the connective tissue due to collagen denaturation, or due
to thrombotic blocking by a thrombus that is formed in the Vasa-Vasorum
because of the thermal damage (the blood flow in these vessels is very
low so it can not cool the blood vessel).

[0256] FIG. 21 illustrates exemplary results for the above. A histology
slide shows analysis and marking of the blocked Vasa-Vasorum with arrows
placed by a trained pathologist in a pig Carotid Artery Vasa-Vasorum in
the adventitia.

[0258] It is believed that the ultrasonic energy absorption is different
for different kinds of tissue and, and furthermore, the content of
collagen fibers may differ.

[0259] Specifically it was shown that in nerve fibers that are wrapped by
fat tissue, it is possible to cause extensive thermal damage to the nerve
tissue, while there is no significant thermal damage in the fat tissue.

[0260] FIG. 22 illustrates two histology slides with analysis and marking
of the thermal damage, or nerve degeneration area made by a trained
pathologist, for a pig renal artery, and nerves in adventitia.

[0261] It is appreciated that certain features of the invention, which
are, for clarity, described in the context of separate embodiments, may
also be provided in combination in a single embodiment. Conversely,
various features of the invention, which are, for brevity, described in
the context of a single embodiment, may also be provided separately or in
any suitable subcombination.

[0262] Although the invention has been described in conjunction with
specific embodiments thereof, it is evident that many alternatives,
modifications and variations will be apparent to those skilled in the
art. Accordingly, it is intended to embrace all such alternatives,
modifications and variations that fall within the spirit and broad scope
of the appended claims. All publications, patents, and patent
applications mentioned in this specification are herein incorporated in
their entirety by reference into the specification, to the same extent as
if each individual publication, patent or patent application was
specifically and individually indicated to be incorporated herein by
reference. In addition, citation or identification of any reference in
this application shall not be construed as an admission that such
reference is available as prior art to the present invention.